We propose a coordinated program of research aimed at the discovery of new tools and tactics for the selective control of insect pests and vectors of disease. In collaboration with two postdoctoral associates the investigation will be carried out on the "tobacco hornworm" (Manduca sexta) - a large lepidopteran cultured throughout the year on a synthetic diet. Our central objective is to identify Insect Growth Regulators which, unlike the presently available juvenile hormone (JH) analogs, can derail the growth of immature larval insects. There are cogent reasons for believing that anti-insecthormones will have this ability. Thus, an anti-JH would oppose or prevent the action of endogenous JH and thereby provoke precocious, lethal methamorphosis. An anti-ecdysone would block larval growth and enforce developmental standstill. Both in vivo and in vitro techniques will be used in the search for anti-hormonal activities. Highest priority will be given to the isolation and characterization of diffusable agents that immature insects use to control during the on-off operation of their own endocrine organs. BIBLIOGRAPHIC REFERENCES: Nijout, H.F., and C.M. Williams, 1974. Control of moulting and metamorphosis in the tobacco hornworm, Manduca sexta (L): Growth of the last-instar larva and the decision to pupate. J. Exp. Biol. 61:481-492. Nijout, H.F., and C.M. Williams, 1974. Control of moulting and metamorphosis in the tobacco hornworm, Manduca sexta (L): Cessation of juvenile hormone secretion as a trigger for pupation. J. Exp. Biol. 61:493-501.